A novel methotrexate-albumin (mtx-rsa)-conjugate causes significant growth delay of o-342 ovarian-carcinoma in-vivo

The increased uptake of native serum albumin in tumors is well described. In previous approaches to use this distribution pattern for tumor therapy, albumin molecules were loaded with maximum quantities of antineoplastic drugs. To preserve the properties of native albumin and to avoid enhanced phagocytotic clearance, we used methotrexate (MTX)-albumin-conjugates with a molar loading ratio of 1:1. In this study we evaluated the effects of single injections of MTX-rat-serum albumin (MTX-RSA) containing 50, 20 and 10 mug MTX on 40 BDIX rats bearing O-342 ovarian carcinoma. Tumor volume post treatment and area-under-the-curve of tumor volumes over treatment were compared with an untreated group using the Mann-Whitney U-test. MTX-RSA treatment caused dose dependent effects and in the 50 mug MTX-dosage significant (P 0.01) growth delay. Additional distribution studies with indirectly radio-iodinated MTX-RSA confirmed the prominent tumor uptake of this compound. We conclude that MTX-albumin-conjugates created with optimized labeling techniques and loading ratios cause significant effects even with very low MTX-doses. Thus these compounds may contribute to enhance the efficacy of MTX-treatment.     

Two Types of Health Care Systems and Their Influence on the Introduction of Perinatal Care: An Epidemiological Twin Model in Berlin from 1950 to 1990

Objectives: When perinatal medicine emerged as a new medical discipline in the 1960s, Berlin was as one of the world's leading centers. During that time, the city was separated into two parts, each fostering its own health care system. After the destruction of the Berlin Wall, it was possible to speak with the citizens of East Berlin and to access their database systems. This created the singular opportunity to objectively compare the development of perinatal care in both parts of Berlin. Methods: Rates of maternal, perinatal, and infant mortality as well as the rate of preterm deliveries were evaluated over time and between East and West Berlin. The timing of introduction of 20 specific perinatal interventions was evaluated across 18 hospitals with more than 500 deliveries (11 in West Berlin and 7 in East Berlin). Interviews were conducted with 100 gynecologists, 100 midwives, and 100 women who had recently delivered their first child from each side of the city regarding their opinions of the importance of these interventions for the quality of perinatal medicine and how they would distribute a budget to improve maternity care. Results: Maternal, perinatal, and infant mortality decreased in both parts of Berlin until 1990 (p<0.0001), without significant differences between East and West Berlin, though the preterm delivery rate was slightly lower in East Berlin compared with West Berlin (p<0.06). Some new clinical techniques and treatments—such as cardiotocography, ultrasound, tocolytic therapy, and peridural anesthesia—were introduced earlier in West Berlin. In contrast, certain public health measures—such as maternal transport, screening programs for diabetes, and support of breastfeeding—were introduced much earlier in East Berlin. There were significant differences between the beliefs of gynecologists, midwives, and mothers in East and West Berlin. In general, citizens of East Berlin were more enthusiastic about technological medical advances, whereas citizens of West Berlin were more supportive of public health and alternative methods. In addition, there were significant differences between female and male physicians in their beliefs about how to improve health care, regardless of whether they resided in East or West Berlin. Conclusions: The results of this study may serve as a basis for reflection on how different social circumstances and health care policies can influence the improvement of maternal and child health care.     

Coronary artery bypass procedures in septuagenarians are justified. Short and long-term results

BACKGROUND: Elective coronary artery bypass surgery can be performed with low operative mortality. There is a controversial discussion whether short-term and long-term results of CABG justify this procedure in elderly patients. METHODS: To add to this discussion, we evaluated retrospectively, the clinical profile, operative technique, short- and long-term results of 1127 patients over 70 years of age who underwent myocardial revascularization between January 1985 and December 1996. RESULTS: Mean age of the cohort was 73.9 years and it rose continuously. In 1996, septuagenarians represented 21.5% of our coronary patients, in comparison to 6.4% in 1985. Analysis of risk factors showed an increasing prevalence of renal failure, obesity, hyperuricemia and a history of smoking. Preoperatively, 87% of our patients were in NYHA-class III or IV, and thus operated to relieve severe symptoms. The percentage of emergent operations decreased over the observed period by 10.3%. The internal mammary artery was used with rising frequency (44.8% in 1985-1992 vs 61.5% in 1993-1996). The number of simultaneous valve replacements increased, too. Postoperatively, we noted a rising incidence of respiratory failure (17.1%) and neurological disorders (13.7%). On the other hand, the need for intra-aortic balloon pumping and hemofiltration declined by 6.6% and 2.9%, respectively. Perioperative mortality (< or =24 hrs) was 3.65%, hospital mortality (< or =30 days) was 9.64%. The actuarial survival (standard error) at 1 year was 82% (+/-4.3%), and 65.7% (+/-3.8%) at 5 years. CONCLUSIONS: Our data suggest that coronary artery bypass grafting can be performed in septuagenarians at an acceptable risk. Since the large majority of patients improve symptomatically, surgery is a recommendable option for a growing number of elderly patients suffering from severe angina.     

Incarcerated postraumatic intercostal lung hernia. Case report and review of the literature

Traumatic lung hernia is a rare diagnosis. A 52-year-old female motorvehicle passenger was admitted as a trauma patient after a motorvehicle accident. She was found to have an incarcerated lung hernia. Size of the hernia, incarceration and respiratory insufficiency mandated immediate surgical intervention with reposition, drainage and stabilisation of the chest wall. The postoperative course was uneventful. The management of the patient is discussed and the available literature reviewed.     

Family and client perspectives on alternative residential settings for persons with severe mental illness

OBJECTIVE: The housing preferences of persons with severe mental illness living in three types of community residences were examined, as were their perceptions of problems in these settings and the relationships between clients' and family members' housing preferences and perceptions of problems. METHODS: A closed-ended questionnaire was developed to gather demographic and diagnostic data and information about housing preferences and seven categories of service-related problems. It was completed by clients who lived in group settings with 24-hour on-site staff, in supported housing with on-site visits by staff, and in homes or apartments with no on-site professional services. Questionnaires were returned by 129 family members and 180 clients. RESULTS: Clients who lived in group settings were significantly more likely to be older, less educated, unemployed, and diagnosed as having schizophrenia than clients in other settings. Although a larger proportion of family members than clients preferred housing with more support, for both families and clients a statistically significant association was found between current and preferred residence. A strong and significant correlation was found between clients' and family members' perceptions of problems, which included stress on the family and clients' social isolation and relapse to illness. For clients who lived independently, a significantly greater proportion of both clients and families reported that social isolation was a problem. CONCLUSIONS: Although supported housing works well for some individuals, a continued need exists for an array of housing with varying levels of structure. The results suggest that clients and families identify the same problems as priorities.     

Effect of patient age on use of the knee joint score

AIM OF THE STUDY: Clinical studies are done with the help of scores though different factors of influence lower comparability. The underlying study examines the influence of patient age as this always presents a certain span. METHOD: 96 degree I damaged knee joints were examined by 3 examiners using the Larson-, Lysholm-, Marshall-, HSS- and OAK-score. Furthermore ratings by a VAS and the Tegner activity score were done. With the Friedman test, the rank correlation coefficient by Spearman and the contingency chart by Bowker it was tested if the examiners and the scores rate equally. To find out the influence of the age three age groups were made up. RESULTS: The examiners judged significantly different excluding the Marshall and the OAK scores. In between two examiners no significant difference could be found between the young and the middle-aged patient group. Between two other examiners no significant difference was found only for the Lysholm and the HSS score in the young group and only for the Lysholm score in the middle-aged group. In the group of the senior patients no significant difference for the scores by Lysholm, Marshall and OAK were found. In the comparison of the second examiner pair no significant differences could be proven by the scores by Larson, the OAK and the HSS. All other comparisons were significantly different. In the comparison of all five scores significant differences were seen between the Larson score and the HSS and the Lysholm and the HSS. The Lysholm score proved to be the strictest, the HSS to be the leanest. CONCLUSION: Especially for the senior patients in dependency of the examiner and the chosen score significant differences were found concluding that the relevance of results lessens for future times as the score results drop with patient age anyway. The age span in one study should have a maximum of 10-20 years to reduce the influence of age on the final result.     

Neuroleptic malignant syndrome during low dosed neuroleptic medication in first-episode psychosis: a case report

 Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal side-effect of antipsychotic drug therapy, especially of dopamine receptor antagonists. As a dose relationship has been postulated, low dose neuroleptization would be expected to help to avoid this side-effect. In contrast, we report on a 21-year-old female following low dose fluphenazine treatment with 2.5 mg/day. The patient recovered from NMS after 3 days of dantrolene administration. Eventually, remission from psychotic symptoms was achieved with clozapine. At 8-month follow-up, psychopathology remained stable and there were no more signs of NMS. Received: 8 July 1998 / Final version: 6 November 1998     

The influence of penetrating keratoplasty and cyclosporin A therapy on MHC class II (Ia)-positive cells in the rat iris and choroid

Background: The presence of Ia-positive cells (MHC class II equivalent) has been previously reported in the iris and choroid of various species. They have been reported to have both round and dendritic morphologies; the latter may represent classic dendritic cells, potent antigen-presenting cells (APCs). It is possible that the dendritic-like cells play a important role in (auto)immune processes of uveal and other ocular tissues. Using the flat or whole mount technique, the distribution of Ia-positive cells in the rat iris and choroid was investigated following penetrating Keratoplasty (PKP) and following treatment with cyclosporin A (CsA). Methods: Lewis (LW) rats received corneal buttons from Lewis-Brown Norway (LW-BN) donors and were randomly assigned to the following groups: (i) operated, untreated (n=24); (ii) operated, CsA-treated (10 mg/kg i.m.;n=22). Controls were groups (iii) normal LW rats (n=13); (iv) unopcrated, CsA-treated (16 days' treatment;n=8); (v) anterior perforation of the anterior chamber (n=3); (vi) eight corneal sutures only (n=4); (vii) syngeneic operated (LW to LW;n=4). Animals of groups (i) and (ii) were killed on the 5th, 9th and 13th postoperative days and on appearance of the corneal rejection (group i, day 13; group ii, day 16). Both eyes were enucleated, immediately fixed, and iris-choroid flat mounts were examined for Ia-positive cells using APAAP immunohistochemistry. Results: In the normal Lewis rat iris, scattered Ia-positive cells of both nondendritic and dendritic morphology were observed. CsA treatment in the unoperated rat did not result in a significant decrease in the percentage of dendritic cells in the iris or choroid. Anterior chamber perforation, the placement of sutures in the cornea and syngeneic PKP resulted in a moderate increase in iris Ia-positive cells. Allogeneic transplantation resulted in a large increase in both types of Ia-positive cells, particularly on day 13 with corneal rejection. In group ii, an initial decrease in Ia-positive cells until day 13 was observed; upon rejection (day 16), the histological picture was similar to that of untreated animals. Alterations in the operated choroid were also apparent following CsA treatment. Conclusion: Corneal transplantation in the Lewis rat results in an increase in Ia-positive cells in the iris; CsA therapy can delay but not prevent this reaction. Changes in choroidal Ia-positive cells following PKP were not apparent, their numbers being affected only by CsA treatment following grafting.     

Pharmacoeconomic evaluation of treatment of penetrating abdominal trauma.

The hospital, pharmacy, and antibiotic costs for patients with penetrating abdominal trauma were compared with reimbursement received; these costs were also analyzed to assess the potential impact of a total prospective pricing system (PPS). During a four-year period, 46 patients admitted solely for penetrating abdominal trauma were retrospectively evaluated: their discharge summaries indicated that, for 9 patients, reimbursement was based on diagnosis-related groups (DRGs) under the PPS; 9 patients had private insurance; and 28 were classified as "self-paying/no insurance." All costs, corrected for inflation, were reported in 1989 dollars. Antibiotics represented 22.5%, 1.7%, and 0.5% of pharmacy, hospital, and DRG reimbursement, respectively; pharmacy costs were 8.5% of hospital costs and 2.3% of DRG reimbursement. For all 46 patients, a net loss of $295 per patient was incurred. Four patients accounted for 43% of the hospital costs. If the hospital had been reimbursed for all of these patients by prospective pricing and DRGs, it would have had a median profit of $9730 in 42 of 46 patients. Costs exceeded DRG reimbursement in the remaining four patients by a median of $8210. Antibiotic costs and pharmacy costs represent a small portion of hospital costs and DRG reimbursement for patients with penetrating abdominal trauma; thus, cost containment efforts in these patients should be directed at other ancillary services and length of stay.